2016 Fiscal Year Final Research Report
Pathological role of mitochondrial oxidative stress in cartilage degeneration
Project/Area Number |
26462319
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Orthopaedic surgery
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Research Institution | Juntendo University |
Principal Investigator |
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Keywords | 酸化ストレス / 軟骨 / 変形性関節症 / 加齢 / 変性 / メカニカルストレス |
Outline of Final Research Achievements |
We herein demonstrate that mechanical loading promoted mitochondrial superoxide generation and selective Sod2 downregulation in chondrocytes in vivo and that mitochondrial superoxide inducer also downregulated Sod2 expression in chondrocytes in vitro. A genetically manipulated model revealed that Sod2 deficiency in chondrocytes also resulted in mitochondrial superoxide overproduction and dysfunction, thus leading to cartilage degeneration. Intra-articular injection of a permeable antioxidant effectively suppressed the mechanical loading-induced mitochondrial superoxide generation and cartilage degeneration in mice. Our findings demonstrate that mitochondrial superoxide plays a pivotal role in the development and progression of osteoarthritis, and the mitochondrial superoxide balance may therefore be a promising target for the treatment of cartilage degeneration.
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Free Research Field |
整形外科
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